[Evaluation of the results of treatment of patients with functional dysphonia using a cepstral test]. / Otsenka rezul'tatov lecheniya patsientov s funktsional'noi disfoniei s pomoshch'yu kepstral'nogo testa.

In order to evaluate the effectiveness of the treatment in patients with functional dysphonia, the Cepstral Peak Prominence (CPP) test was used. Twenty dysphonic women aged from 18 to 47 years were under observation. The control group consisted of 20 healthy women of close age. Patients underwent 5-7 sessions electrostimulation of laryngeal muscles and phonopedic treatment, after which a complete restoration of the voice was noted. The Praat clinical program was used, installed on a Hewlett-Packard 630 laptop (Pentium B960, 2.2 GHz). A SHURE SM94 condenser microphone was used as well. In the control group, the results were as follows: M=7.49 (SD=1.26) dB. In the main group before treatment: M=5.00 (SD=1.07) dB, after treatment: M=7.95 (SD=1.34) dB. Differences in KT values in the main group before and after treatment (5.00 dB and 7.95 dB, respectively) were significant at p<0.0001. Differences in KT values in the main group before treatment (5.00 dB) and in the control group (7.49 dB) were significant at p<0.0001. Differences in KT values in the main group after treatment (7.95 dB) and in the control group (7.49 dB) were not significant at p>0.05. The study showed high sensitivity of the method. The CPP data after treatment were higher than those before treatment and did not differ from the control ones. It is concluded that CPP is a highly sensitive method for evaluating the degree of periodicity of an acoustic signal and can be used to evaluate the effectiveness of treatment in patients with functional dysphonia.

[FROM "CAPRICE MEDICINE" TO "EQUAL RESPONSIBILITY MEDICINE": TASKS, TECHNOLOGIES AND SPECIFICS OF CONFLICT MANAGEMENT IN A MULTIDISCIPLINARY PRIVATE CLINIC].

The article substantiates the tasks of introducing a conflict management system into the work of a private sector medical organization, reducing the number of ethical and legal conflicts that arise during the provision of medical care. The analysis of the conceptual foundations, regulatory framework and specifics of the use of conflict management tools in the context of solving organizational and managerial tasks in a private multidisciplinary clinic is presented.

[The analytical review of normative and organizational support of functioning of perinatal service in The Russian Federation in 2000-2020].

The formation of code of normative legal documents ensuring activities of perinatal service is one of the most important, basic organizational technologies that determine activities of obstetrics and childhood services, contributing to increasing of natality, decreasing of maternal and infant morbidity, and maternal and childhood health care in general. The article presents analysis of formation of normative legal base that regulates functioning of perinatal service in the Russian Federation in 2000-2020. Actually, there is no objective prerequisites for fundamental alterations in the three-level system of medical care of women during pregnancy, labor, postpartum period and newborns. However, the regulatory adjustment of the system, improvement and refinement of models of profile patients' routing, development of medical care of pregnant women, parturient women and puerpera will proceed.

[On the Methodology of Studying Organizational Technologies of Health Preservation].

The article considers methodological studying of problematics of health preservation and its organizational technologies. The health preservation is considered in the context of public health policy. The necessity of complex interdisciplinary and longitudinal approach to studying this problematic is substantiated. The results of analysis of semantics of key concepts of health preservation are presented. The patient-centralized principles of activities and communication as applied to health preservation are substantiated. The differentiation between concepts of "value" and "utility" of organizational technologies of health preservation for health are discussed. The possible areas of studying positioning of health preservation in the system of personality values, including health culture, are proposed. The possible structuration of factors determining health condition and healthy life-style are proved. The scope of principles and approaches for subsequent elaboration of methods, standards, instruments and regulations of complex methodology of studying issues of health preservation and its organizational technologies are established.

[MEDICAL AND LEGAL ASPECTS IN PROOF OF RAPES].

The purpose of the study is to analyze new edition of the article 152 of the Criminal Code of Ukraine «Rape¼, which was adopted with the aim of implementing the Council of Europe Convention on preventing and combating violence against women and domestic violence. The analysis was carried out in terms of the possibility of implementing legal definitions in evidence, taking into account the fundamental medical scientific provisions related to sexual relations. The authors, taking into account the study of more than 100 sentences handed down by the courts of Ukraine in 2010-2018 in criminal cases of rape from the point of view of using medical knowledge in evidence, found a significant change in the objective side of rape, which affected the subject of evidence in criminal proceedings. Now rape is defined as committing acts of a sexual nature associated with vaginal, anal or oral penetration into the body of another person using the genitals or any other object, without the voluntary consent of the victim. A significant change in the rape modus operandi leads to a number of problematic issues in the practical application of these provisions by law enforcement agencies and courts. These issues can be solved, according to the authors' opinion, only by taking into consideration medical and legal aspects of rape. The medical aspect of rape is very important because the concept of rape is legal, but its interpretation is based on the use of medical concepts. The concept of "committing acts of a sexual nature associated with vaginal, anal or oral penetration into the body of another person using the genitals or any other object" is analyzed taking into account the existing and well-established in Forensic Medicine notions of sexual intercourse. The legal aspect of rape is not only to give a legal interpretation of the medical facts of committing sexual acts, but also to establish the absence of the voluntary consent of the victim. The problem of false statements about rape is analyzed, possible indicators of such statements are identified. This problem is quite topical in many countries with a similar interpretation of rape. It is concluded that the medical and legal aspects of rape are closely interrelated, since mechanism of this crime is based on physiological sexual act that is subject to legal assessment.

Development of a polyclonal antibody-based indirect competitive ELISA for the determination of tetrodotoxins in marine ribbon worms (NEMERTEA) and its comparison with high performance liquid chromatography-tandem mass spectrometry.

Tetrodotoxin (TTX) is a potent neurotoxin frequently occurring in marine organisms along with its numerous analogues. To determine the total TTX content, we developed an enzyme-linked immunosorbent assay (ELISA) technique utilizing polyclonal antibodies against TTX. The technique was tested using extracts of marine worms of the phylum Nemertea and confirmed by HPLC-MS/MS. It proved to be suitable for a preliminary assessment of the toxicity of marine organisms.

Detection of Ehrlichia spp. and Theileria spp. in Hyalomma anatolicum ticks collected in Tajikistan.

The objectives of our study were to survey the prevalence of genetic markers for Rickettsia spp., Ehrlichia spp., Anaplasma spp., Babesia spp., and Theileria spp. in Hyalomma anatolicum ticks collected in southwestern Tajikistan and to perform sequencing and phylogenetic analysis of fragments of the 16S rRNA gene and groESL operon from Ehrlichia spp. and fragments of the 18S rRNA gene of Theileria spp. detected in H. anatolicum ticks. Hyalomma anatolicum ticks collected in the Tursunzade and Rudaki districts of Tajikistan were tested for DNA of Rickettsia spp., Ehrlichia spp., Anaplasma spp., Babesia spp., and Theileria spp. by PCR with specific primers. The amplified fragments were sequenced and analyzed. DNA of Ehrlichia spp. (3.3 %) and Theileria spp. (3.3 %) was detected only in H. anatolicum ticks collected from the Rudaki district, and DNA of Ehrlichia spp. (0.7 %) was found in H. anatolicum ticks from the Tursunzade district. Sequence analysis of fragments of the 16S rRNA gene and groESL operon from Ehrlichia spp. revealed high similarity to Ehrlichia spp. The Tajik isolates of Theileria spp. were genotyped as Theileria annulata based on the analysis of 18S rRNA gene sequences. The phylogenetic analysis demonstrates that Ehrlichia spp. isolates are highly similar to Ehrlichia spp. circulating in China and Brazil. The isolate Tajikistan-5 is closely related to the putative novel species Ehrlichia mineirensis. The Tajik isolates of Theileria spp. were clustered with T. annulata isolates from Turkey, Iran, Pakistan, and China by phylogenetic analyses.

Concentration of viruses and electron microscopy.

Nearly all lethal viral outbreaks in the past two decades were caused by newly emerging viruses. Viruses are often studied by electron microscopy (EM), which provides new high-resolution data on the structure of viral particles relevant to both fundamental virology and practical pharmaceutical nanobiotechnology. Electron microscopy is also applied to ecological studies to detect viruses in the environment, to analysis of technological processes in the production of vaccines and other biotechnological components, and to diagnostics. Despite the advances in more sensitive methods, electron microscopy is still in active use for diagnostics. The main advantage of EM is the lack of specificity to any group of viruses, which allows working with unknown materials. However, the main limitation of the method is the relatively high detection limit (107 particles/mL), requiring viral material to be concentrated. There is no most effective universal method to concentrate viruses. Various combinations of methods and approaches are used depending on the virus and the goal. A modern virus concentration protocol involves precipitation, centrifugation, filtration, and chromatography. Here we describe the main concentrating techniques exemplified for different viruses. Effective elution techniques are required to disrupt the bonds between filter media and viruses in order to increase recovery. The paper reviews studies on unique traps, magnetic beads, and composite polyaniline and carbon nanotubes, including those of changeable size to concentrate viral particles. It also describes centrifugal concentrators to concentrate viruses on a polyethersulfone membrane. Our review suggests that the method to concentrate viruses and other nanoparticles should be chosen with regard to objectives of the study and the equipment status of the laboratory.

H2S-Mediated Changes in Erythrocyte Volume: Role of Gardos Channels, Na+,K+,2Cl- Cotransport and Anion Exchanger.

The effect of H2S on changes in erythrocyte volume was studied by spectrophotometrical and potentiometric methods. It was found that H2S donor NaHS (2.5, 10, and 100 µM) induced an increase in erythrocyte volume in heterosmotic media. Activation of Gardos channels with A23187 or ascorbate-phenazine methosulfate system causes erythrocyte shrinkage and hyperpolarization of their membrane, while addition of NaHS restored erythrocyte volume. The decrease in erythrocyte volume upon blockade of Na+,K+,2Cl- cotransporter (bumetanide) or anion exchanger (SITS) was abolished by H2S donor NaHS, which attested to an important role of these transporters and chlorine conductivity of the membrane in the maintenance of the homeostasis of blood cells.

Role of Carbon Monoxide in the Mechanisms of Action of Extracellular ATP on Contractile Activity of Vascular Smooth Muscle Cells.

We studied the role of carbon monoxide (CO) in the effect of P2X and P2Y receptor agonist ATP on the tone of rat aorta segments with intact endothelium. ATP (1-1000 µM) and P2X receptor agonist α,ß-MeATP (100 µM) relaxed segments precontracted with phenylephrine (10 µM), while UTP (100-1000 µM) increased the amplitude of phenylephrine-induced contraction. The relaxing effect of ATP was enhanced by CORM II (100 µM), NO synthase inhibitor L-NAME, and guanylate cyclase inhibitor ODQ and attenuated by ZnPP IX (100 µM). The constrictive effect of UTP was weakened by CORM II (100 µM), but was not changed by ZnPP IX (100 µM). ZnPP IX (100 µM) weakened the relaxation response to α,ß-MeATP. Thus, ATP involves the CO-dependent signaling cascade through P2X receptors.

[The medical ethical aspects of organization of medical rehabilitation].

The article considers such aspects of organization of medical rehabilitation care of population as accessibility, quality, social efficiency from perspective of medical ethics. The quality of diagnostic, prevention and treatment of diseases is affected by qualification of medical personnel that is applied both to areas of clinical medicine and health care management. The specialists are to apply common principles and standards of health care. Among them are support of valuable quality of medical care under optimal application of available resources and observance of medical ethics standards. The Republic of Dagestan is anagrarian region where 55% of population resides in rural area and most of health care resources are cumulated in urban area. The indices of health of population residing in rural area are in many parameters worse than in urban population and provision of medical institutions with medical personnel is low. The specialized medical care support including medical rehabilitation, of rural population, is provided without additional managerial decisions and is much more difficult as compared with patients residing in urban area. Hence in conditions of necessity of optimization of resource support of health care system functioning no extensive development of possibilities of medical rehabilitation is possible in rural residents of Dagestan.

Cytokine Profiling of Subclinical Tick-Borne Infections in Humans.

Over many years, tick-borne infections remain one of the most serious threats to human health worldwide. The immune response to these infections in a human after confirmed bite by an infected carrier at the early stages of infection in the absence of clinical symptoms can be the first indicator of the presence of the infectious agent in the body. During viral infection, the concentration of IL-1α, IL-8, IL-10, IL-17A, and IFNγ increases; superoxide dismutase also increases, in contrast to bacterial infections. A slight decrease in the concentration is observed only for receptor antagonist IL-1Ra. During the infection caused by bacterial pathogens, very similar profiles of the innate human immune response are observed: activation of IL-1α, IL-8, and IFNα and suppression of superoxide dismutase, IL-1Ra, and IL-17A production. It has been demonstrated, that the immune response is triggered immediately after infection, and changes in the concentration of the main cytokines in the blood plasma can be detected as early as on days 2-5 after tick bite. These results can be useful in developing new methods of emergency diagnosis and prevention of tick-borne infections.

Early Deсline in Rat Soleus Passive Tension with Hindlimb Unloading: Inactivation of Cross-bridges or Activation of Calpains?

The study was aimed at testing the hypotheses about the role of cross-bridges and calpains in reduction of rat soleus passive tension under conditions of hindlimb unloading. For this purpose, we used an inhibitor of µ-calpain PD 150606 as well as a blocker of actomyosin interaction (blebbistatin). It was found for the first time that a decrease in passive tension of rat soleus after 3-day hindlimb unloading is associated with the activity of µ-calpain and does not depend on the processes of cross-bridges formation.

[Markers of gluten intolerance in children with autism spectrum disorders and Down'syndrome]. / Markery neperenosimosti gliutena u detei s rasstroistvami autisticheskogo spektra i sindromom Dauna.

AIM: To study serological and genetic markers of gluten intolerance in children and teenagers with autism spectrum disorders (ASD) and Down's syndrome (DS). MATERIAL AND METHODS: Thirty-three children with ASD (group 1) and 8 with DS (group 2), aged from 2.5 to 15 years, were examined. There were 27 boys and 6 girls in group1, 5 boys and 3 girls in group 2. Most of the children were on a regular diet and only 4 children with ASD kept gluten-free diet (GFD). Using ELI method antibodies to gliadin IgG (AntiGliadin IgG), antibodies to deamidated peptides of gliadin IgA (AntiDGP IgA), immunoglobulin A (IgA) were identified. Haplotypes HLA-DQ2 and DQ8 were determined using PCR. RESULTS: AntiGliadin IgG were identified in 12.1% (4) patients of group 1, with the exception of patients on GFD in 13.8%, and in 50% patients of group 2. One child with ASD had selective IgA deficiency. Haplotypes predisposing to celiac disease had 41.9% of patients of group 1 and 37.5% of patients of group 2. In ASD, the distribution of genotypes was as follows: DQ2 (64.3%), DQ8 (28.6%), DQ2/DQ8 (7.1%,). In DS, all patients had haplotype DQ2. AntiDGP IgA were not identified in both groups. CONCLUSION: The predominant form of gluten intolerance in children with ASD and DS is sensitivity to gluten, which can be identified in 40-50% of patients. Celiac disease, an autoimmune form of gluten intolerance, can be diagnosed in single cases, although predisposition to it is identified in 41.9% - 37.5% patients with ASD and DS, respectively. Before the start of GFD, laboratory tests should be made to identify forms of gluten intolerance and the use of GFD.

['Masks' of acute neuroinfections and markers of differencial diagnosis]. / 'Maski' ostrykh neiroinfektsii i markery differentsial'noi diagnostiki.

AIM: To compare thе medical history, clinical features, composition of cerebrospinal fluid (CSF), results of laboratory and instrumental examinations of patients with acute neuroinfections and differentiable diseases including a pseudoinflammatory variant of the acute stage of uncomplicated subarachnoid hemorrhage (SAH), consequences of traumatic brain injury (traumatic SAH, SAN combination with secondary purulent meningitis, posttraumatic nasal liquorrhea, intracerebral hematomas), abscesses and tumors of the brain, lymphoma with proven CNS. These diagnoses were mistakenly made to patients admitted to an infectious department. MATERIAL AND METHODS: Forty-six patients, aged from 18 to 83 years, hospitalized in the Department of neuroinfections and intensive care in 2010-2016 were examined. Conventional clinical neurological, laboratory, instrumental (including MRI) examinations of patients, comprehensive examination of CSF samples, the study of markers of inflammation (C - reactive protein, CSF lactate), immunophenotyping of CSF cells were performed. RESULTS AND CONCLUSION: The misdiagnosis can be explained by the overestimation of such symptoms as the acute (in most cases) onset of the disease with increased body temperature to febrile levels, presence of meningeal syndrome, disorders of consciousness and focal symptoms of varying severity. The authors showed the errors and difficulties in the diagnosis, the role and importance of an integrated, interdisciplinary approach taking into account history, clinical data, results of CSF study, conventional and special methods of laboratory and instrumental examination of patients.

Molecular Mechanisms of Action of Gas Transmitters NO, CO and H2S in Smooth Muscle Cells and Effect of NO-generating Compounds (Nitrates and Nitrites) on Average Life Expectancy.

Gaseous signaling molecules (gas transmitters) take an especial position among the numerous signaling molecules involved in the regulation of both intracellular processes that occur in different types of cells and cell-cell interactions. At present time, gas transmitters include three molecules whose enzymatic systems of synthesis and degradation, physiological action and intracellular effectors, the change of which under the action of gas transmitters may result in physiological and/or pathophysiological effects are well- determined. These molecules include nitrogen oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). They are involved in the regulation of functions of various organs and systems of the human body, including the circulatory system. Interaction of NO, CO and H2S with various enzymatic and structural components of endothelial and, especially, smooth muscle cells has a significant impact on vascular tone and blood pressure. Furthermore, the crossing of NO-, CO- and H2S-mediated signaling pathways at common effectors and interaction with each other can determine the end, resulting functional response of the cell. The knowledge of the molecular targets of gas transmitters' action, the structure of the binding centers for gas transmitters and their interaction with each other may be essential in the development of methods of regulation of these signaling systems by targeted, directed action. This review summarizes the molecular mechanisms of the NO, CO and H2S interaction with the main targets, which carry out their regulatory effect on vascular smooth muscle cells. Also we describe here different ways of cross-regulation of NO-, CO- and H2S-dependent signaling pathways. We analyzed NO-synthase and nitrite reductase systems of nitric oxide cycle and discuss the nitrate-nitrite background of the existence of modern man, which can substantially modify the signaling system, the metabolism of virtually all cell ultrastructure of neurons, neuron-neuron and neuron-glial interactions and exerts its influence on socially significant diseases that can affect the quality and the average life expectancy.

Regulation of Contractile Responses of Vascular Smooth Muscle Cells under Conditions of Hypoxia-Reoxygenation.

We analyzed the effects of hypoxia and reoxygenation on changes in contractile activity in rat aortic smooth muscles. Both hypoxia and reoxygenation induced relaxation of smooth muscle cells precontracted with high-potassium Krebs solution (30 mM KCl) or α1-adrenoceptor agonist phenylephrine. Vasodilation resulted from enhancement of potassium permeability of smooth muscle cell membranes caused by activation of voltage-gated potassium channels (triggered by both precontracting agents) or by opening of ATP-sensitive potassium channels (phenylephrine). In isolated smooth muscle cells, both hypoxia and inhibition of Na+,K+-ATPase with ouabain led to depletion of intracellular store of macroergic substances, reduced potassium concentration, and elevated the content of sodium ions.

[Secretion of Phenolic Compounds into Root Exudates of Pea Seedlings upon Inoculation with Rhizobium leguminosarum bv. viceae or Pseudomonas siringae pv. Pisi].

The content of apigenin, naringenin, pisatin, dibutyl-ortho-phthalate, and N-phenyl-2-naphthyl-amine were assayed in root exudates of pea (Pisum sativum L.) seedlings one day after their inoculation with Rhizobium leguminosarum, bv. viceae or Pseudomonas siringae pv. pisi, which represent, respectively, mutualistic and antagonistic strategies of interaction with a host plant. After inoculation with either bacteria, the concentrations of apigenin and pisatin in the root exudates were equal, whereas the concentrations of naringenin and N-phenyl-2-naphthylamine were different and those of dibutyl-o-phthalate were unchanged. A certain role is suggested for the phenolic compounds in an accomplishment of symbiotic relations of bacteria with a host plant.

[The results of cochlear implantation in the patient with hereditary and non-hereditary hearing loss]. / Rezul'taty kokhlearnoi implantatsii u patsientov s nasledstvennymi i nenasledstvennymi formami tugoukhosti.

The objective of the present study was to evaluate the effectiveness of rehabilitation of the patients after cochlear implantation in the early and late periods after operation taking into consideration the etiology of congenital deafness. The comprehensive clinico-audiological examination performed during the period from 2010 to 2015 involved 246 children who had undergone cochlear implantation (CI). All children were operated at the National Research Center for Audiology and Hearing Rehabilitation in the period from 2003 to 2013. 83 (56%) patients were aged 1 to 3 years at the time of surgery. Their age varied from 3 to 18 years when they underwent the clinico-audiological examination. Thus, the study is based on the experience with cochlear implantation varying from 3 to 12 years. The genetic analysis revealed mutations in the GJB2 gene in 49% of the children, in agreement with the data of earlier studies. 85% of all the children with GJB2 deafness surgically treated at the age under 4 years attend ordinary institutions of learning. Within 24 months after the onset of the observations the majority of the children with hereditary deafness (63%) were referred to the groups with good and excellent results of the rehabilitation and only 6 (12%) patients presented with unsatisfactory results. It was shown that the acquired causes of the loss of hearing including severe prenatal pathology have a negative influence on the long-term outcomes of rehabilitation. The results of the genetic analysis for the elucidation of the cause of impaired hearing can be employed as a prognostic criteria not only for the prediction but also for the guarantee of the success of cochlear implantation provided the rehabilitative process was initiated in a proper time.